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Association of a GTP-binding protein Goα subunit mutation with schizophrenia

Molecular Psychiatry volume 6, page 359 (2001)Cite this article

SIR – The pathogenesis of schizophrenia has been suggested to involve not only dopaminergic overactivity but also abnormal function of signaling systems associated with second messengers.1 Goα is a member of the α subunit family of GTP-binding proteins (G proteins), and interacts with muscarinic cholinergic, γ-aminobutyric acid B, and dopamine D2 receptors.2 Tsukamoto et al3 reported the sequence of human Goα genomic DNA. In the present study, we hypothesized that mutations in the Goα gene may be associated with the pathogenesis of schizophrenia.

We investigated 175 unrelated Japanese patients (92 men and 83 women; mean age = 47.3 years, SD = 12.1) who met DSM-IV criteria for schizophrenia; 172 unrelated control subjects (76 men and 96 women; mean age = 41.8 years, SD = 12.7) were also studied. Written informed consent was obtained from all probands according to a research protocol approved by the ethics committee of Osaka City University Medical School. Using single strand conformational polymorphism (SSCP), one missense mutation, ATG→ACG (Met129→Thr129) in exon 4, and two silent mutations, ACT→ACC (Thr171) in exon 5 and AAA→AAG (Lys317) in exon 8B, were found in the Goα gene among patients with schizophrenia. The genotype distribution for each mutation was not significantly different from the distribution expected according to Hardy–Weinberg equilibrium. While silent mutations were not associated with schizophrenia (data not shown), significant excesses of the missense mutation in genotype (P = 0.012, χ2 = 6.313, df = 1) and allele frequencies (P = 0.013, χ2 = 6.193, df = 1) were found in patients compared with controls (Table 1).

Table 1 Genotype and allele frequencies of a new missense mutation ATG→ACG (Met129→Thr129) in exon 4 of the Goα protein gene in schizophrenic patients and controls
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Authors and Affiliations

  1. Department of Neuropsychiatry, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    M Tani & N Kiriike

  2. Department of Neuropsychiatry, Osaka City Kosaiin Hospital, 6-2-1, Furuedai, Suita-city, Osaka, 565-0874, Japan

    K Mui

  3. Department of Neuropsychiatry, Kijima Hospital, 892, Mori, Kaizuka-city, Osaka, 597-0044, Japan

    Y Minami

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  1. M Tani
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  2. K Mui
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  4. N Kiriike
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Correspondence to K Mui.

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Tani, M., Mui, K., Minami, Y. et al. Association of a GTP-binding protein Goα subunit mutation with schizophrenia. Mol Psychiatry 6, 359 (2001). https://doi.org/10.1038/sj.mp.4000913

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